It is planned to perform an in-depth analysis of IL-2 pathophysiology in human immunodeficiency syndromes (IDS). These studies will focus on the following diagnostic categories as well as on appropriate controls: (1)\congenital IDS; (2)\IDS of unknown etiology: (a)\CVI and (b)\AIDS with and without Kaposi's sarcoma; (3)\therapy/cancer-associated IDS: (a)\Hodgkin's disease prior to and after therapy, (b)\ovarian carcinoma prior to and after high-dose chemotherapy, (c)\breast cancer prior to and on adjuvant chemotherapy, and (d)\patients prior to and after allogeneic and autologous bone marrow transplantation. The in vitro studies planned will evaluate IL-2 production and response (IL-2 P/R) of total mononuclear cell fractions (PBL) as well as of isolated PBL subsets. We will investigate: (1)\the molecular events leading to T-cell activation by analysis of (a)\methylation patterns of the IL-2 gene, (b)\IL-2m RNA blots, (c)\demonstration of IL-2 in individual cells by immunofluorescence, (d)\quantitation of IL-2 secreted into the culture medium, (e)\IL-2 receptor (Tac) expression by immunofluorescence, and (f)\expression of other cell surface structures related to T-cell activation and/or proliferation (e.g., HLA-Dr, transferrin receptor); (2)\the effect of other cell types on IL-2 P/R, e.g., monocytes, NK cells, suppressor and helper T cells through mixing experiments of PBL subsets; (3)\the role of other lymphokines (e.g., interferon alpha, gamma, interleukin 1) and pharmacological agents (e.g., cimetidine, indocine, cyclosporin A) on IL-2 P/R of PBL and PBL subsets; (4)\the biological effect of monoclonal reagents recognizing antigens of regulatory significance in IL-2 physiology (e.g., anti IL-2, anti IL-2 receptor, OKT3, antitransferrin receptor, anti Ia, anti HLA) on IL-2 P/R of PBL and PBL subsets. It is hoped that the understanding of the molecular events regulating IL-2 and Tac expression and definition of specific defects in IDS will allow their specific modulation in vitro and eventually in vivo. (IS)